Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
PLoS Negl Trop Dis. 2012;6(2):e1492. doi: 10.1371/journal.pntd.0001492. Epub 2012 Feb 14.
(•)NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigate the role of ROS in T. cruzi infection, mice deficient in NADPH phagocyte oxidase (gp91(phox) (-/-) or phox KO) were infected with Y strain of T. cruzi and the course of infection was followed. phox KO mice had similar parasitemia, similar tissue parasitism and similar levels of IFN-γ and TNF in serum and spleen cell culture supernatants, when compared to wild-type controls. However, all phox KO mice succumbed to infection between day 15 and 21 after inoculation with the parasite, while 60% of wild-type mice were alive 50 days after infection. Further investigation demonstrated increased serum levels of nitrite and nitrate (NOx) at day 15 of infection in phox KO animals, associated with a drop in blood pressure. Treatment with a NOS2 inhibitor corrected the blood pressure, implicating NOS2 in this phenomenon. We postulate that superoxide reacts with (•)NO in vivo, preventing blood pressure drops in wild type mice. Hence, whilst superoxide from phagocytes did not play a critical role in parasite control in the phox KO animals, its production would have an important protective effect against blood pressure decline during infection with T. cruzi.
（•）NO 被认为是感染克氏锥虫期间巨噬细胞衍生的关键细胞毒性效应物。另一方面，活性氧（ROS）的杀菌特性是众所周知的，但在体内感染克氏锥虫时，它们的重要性却被低估了。为了研究 ROS 在克氏锥虫感染中的作用，用 Y 株克氏锥虫感染 NADPH 吞噬细胞氧化酶缺陷（gp91(phox)（-/-）或 phox KO）小鼠，并跟踪感染过程。与野生型对照相比，phox KO 小鼠的寄生虫血症、组织寄生虫病、血清和脾细胞培养上清液中的 IFN-γ 和 TNF 水平相似。然而，所有 phox KO 小鼠在接种寄生虫后 15 至 21 天内都死于感染，而 60%的野生型小鼠在感染 50 天后仍存活。进一步的研究表明，phox KO 动物在感染第 15 天血清中硝酸盐和亚硝酸盐（NOx）水平升高，同时血压下降。用 NOS2 抑制剂治疗可纠正血压，表明 NOS2 参与了这一现象。我们推测超氧阴离子与（•）NO 在体内反应，防止野生型小鼠血压下降。因此，虽然吞噬细胞产生的超氧阴离子在 phox KO 动物中对寄生虫控制没有关键作用，但在感染克氏锥虫期间，其产生对血压下降会有重要的保护作用。
